SummaryRecent evidence indicates that human neutrophils can serve as non-professional antigen presenting cells (APC). Although expression of MHC class II and co-stimulatory molecules on human neutrophils is limited, these molecules can be significantly induced following in vitro exposure to the cytokines IFNγ and GM-CSF. Since professional APCs such as dendritic cells express both costimulatory and co-inhibitory molecules for activation and regulation of adaptive immunity, we determined whether cytokines induce increased expression of specific co-signaling molecules on human neutrophils. We report here that circulating human neutrophils express co-inhibitory molecules such as immunoglobulin-like transcript (ILT) 4 and 5, and also comparatively low and highly variable levels of ILT2 and 3, but the expression of these ILTs was not significantly changed by cytokine treatment. In contrast, we demonstrate for the first time that human peripheral blood neutrophils, although do not express the co-inhibitory molecule, programmed death ligand (PD-L) 1 on their surface, can express this molecule at moderate levels following cytokine exposure. Although moderate PD-L1 levels on healthy volunteers' neutrophils were not inhibitory to T cells, our findings do not exclude a possible robust increase in neutrophil PD-L1 expression in pathological conditions with immunosuppressive functions. These results suggest a possible immunoregulatory role for human neutrophils in adaptive immunity. KeywordsHuman neutrophil; PD-L; ILT; Cytokine Corresponding Author: Asit K. De, Ph.D. or Paul E. Bankey, M.D., Ph.D., Department of Surgery, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. asit_de@urmc.rochester.edu or paul_bankey@urmc.rochester.edu, Phone: (585) 273-1934, Fax: (585) 276-2384. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access IntroductionAlthough the role of polymorphonuclear neutrophils (PMN) in innate immunity is well established, their role in stimulating or regulating T cell functions is not well characterized [1,2]. In order to maintain homeostatic balance in the adaptive immune response, professional antigen presenting cells (APC) such as monocytes (MO) and dendritic cells (DC) express MHC class II and co-stimulatory molecules for signaling T cell activation and co-inhibitory molecules for inhibiting T cell activation [3,4]. In contrast to the well accepted role of MO and DC in the initiation and maintenance of adaptive immunity, the participation of human neutrophils, the most abundant circulating leukocyte population, in adapt...

With the increased use of chest computed tomography (CT) scan in the initial evaluation of major trauma, findings that were not seen on a chest radiograph (CXR) are increasingly identified. Pneumomediastinum (PM) seen on CXR in blunt trauma patients is considered worrisome for airway and/or esophageal injury. The purpose of this study was to determine the incidence and clinical significance of PM found on CT in blunt trauma patients. Blunt trauma patients admitted to a single Regional Trauma Center over a 2-year period were identified. Records were reviewed for demographics, mechanism, diagnostic evaluations, injuries, and outcome. A total of 2052 patients met study criteria. Fifty-five (2.7%) had PM; 49 patients (89%) had PM identified on CT alone, whereas six patients (11%) had it identified on both CXR and CT. There was no significant difference in gender or age between the two groups. Associated injuries were similar between groups. No patients had tracheobronchial or esophageal injuries. In this study, PM seen on CT was found to have little clinical significance other than as a marker for severe blunt trauma. No patients with airway or esophageal injuries were seen in any of the PM patients.

The transfusion of ABO non-identical platelets is an accepted practice, involving infusion of antigen and/or antibody that is ABO incompatible with the recipient. This results in the formation of high molecular weight immune complexes, which could, in theory, adversely affect platelet and coagulation factor function. Studies have demonstrated putative deleterious effects of ABO non-identical transfusions. In cardiac surgery patients receiving ABO non-identical platelets required 50% more red blood cell (RBC) transfusions than those who received only ABO identical platelets (Transfusion41:790, 2001). Furthermore, blood group O and A patients have genetically determined lower levels of von Willebrand factor (vWF) than B and AB patients (Blood69:1691,1987), and might be expected to have more bleeding and require more RBC transfusions. Our institution implemented a protocol of transfusing only ABO identical components in April, 2005. We report here the potential effects of transfusing ABO non-identical platelets, by comparing RBC usage in surgical patients before and after introduction of a protocol of “only ABO identical” transfusions. We also report the role of ABO blood group in red cell usage. Because non-group O trauma patients by necessity receive group O red cells we excluded them from this analysis. Transfusion records for all non-trauma surgical patients receiving any platelet transfusions for one year after April, 2005 were reviewed. Patients receiving only ABO identical platelet transfusions were analyzed by blood groups: B/AB versus O/A. Group B/AB patients (n=72) required a mean of 12.5 +/− 11.7 RBCs, whereas group A/O patients (n=313) required 17.8 +/− 20.5 (p=0.036). These findings are the reverse of the patient populations receiving a mixture of ABO identical and non-identical platelets prior to April, 2005, before the implementation of an “ only ABO identical” transfusion policy. Group B/AB patients, who received more ABO non-identical platelet transfusions than A/O patients (mean 7.5 +/− 11 versus 3.3 +/− 6.2, p=0.0001), required significantly more RBCs (mean 19 +/− 25 versus 13 +/− 13, p=0.0086). Amongst those receiving only ABO identical transfusions group O patients required the largest number of RBCs, (mean 19.6 +/− 24.1), followed by A (16.0 +/− 15.8, p=0.096), B (13.2 +/− 13.1, p=0.041), and AB (11.2 +/− 7.8, p=0.05). One plausible explanation is that blood group O patients have the lowest levels of vWF and other clotting factors, while AB patients have the highest levels (AB > B > A > O). Our data in recipients of ABO identical transfusions confirm findings in the literature that group O patients may be at greater risk of hemorrhage than groups B and AB patients. However, when ABO non-identical platelets are transfused, significantly more bleeding is seen in group AB and B patients than in group O patients. We hypothesize that ABO non-identical transfusions may impair, rather than improve, hemostasis in some patients. RBC Usage (Units) Pre and Post ABO Identical Only Policy Blood Groups A/O Blood Groups B/AB P-Value Pre-ABO Identical Only Policy 13 +/− 13 19 +/− 25 0.0086 Post-ABO Identical Only Policy 17.8 +/− 20.5 12.5 +/− 11.7 0.036

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